This program is directed towards understanding the molecular mechanisms in PUVA therapy (psoralen plus near-UV radiation) or psoriasis, and other human skin diseases and photodynamic therapy of malignant tumors, with the objective of identifying factors that may improve the efficacy of current clinical procedures. Liposomes and resealed red blood cell membranes will be used to study singlet oxygen generation by furocoumarins currently employed as PUVA sensitizers, and the effects of dark-complexing of the furocoumarin to DNA and of covalent photobinding to DNA on this process. The results will be extended to repair-competent cellular systems by means of mathematical modeling. This phase of the program should provide new information about the relationships between the initial molecular pathways and biological endpoints. A second phase of the program will emphasize the preparation and properties of photosensitive liposomes, including their potential role as drug carriers in photodynamic therapy with hematoporphyrin sensitizers. Studies will be made on photosensitization of liposomes to hydrodynamic stress and the damage to entrapped model compounds and drugs. This work will include the investigation of photosensitization by the clinical hematoporphyrin derivative, HPD, using laser flash photolysis and probe techniques for the involvement of the active oxygen intermediates.